Changes that may occur in the expression of protein and mRNA for TGF-beta isoforms in response to various disease states and tissue treatments are being investigated using immunohistochemistry and Northern blot techniques. For example, there is an increase in expression of TGF-beta1 protein in prostatic carcinoma, as compared to benign prostatic hyperplasia, in both humans and in a mouse model of the disease. There is also increased expression of extracellular TGF-beta1 protein in human breast cancer following tamoxifen treatment. Following heat shock of rats, there are transient increases in TGF-betas in the heart which may mediate the cardioprotective effects of heat shock. This hypothesis is being investigated by measuring recovery of contractile force following ischemia-reperfusion in an isolated perfused heart system. This is being done in hearts from rats exposed to heat shock, as well as in control animals in the presence or absence of TGF-beta or TGF-beta antibodies. Some of the cardioprotective effects of TGF-beta may be mediated by decreased levels of oxygen free radicals. In endothelial cells, it appears that TGF-beta can decrease mRNA expression of xanthine oxidase which is involved in generation of oxygen free radicals. The actions of TGF-beta in the heart during septic shock are also being investigated. Lipopolysaccharide (LPS) treatment of rats causes destruction of the collagen ultrastructure of the heart as determined by scanning electron microscopy and the ability of TGF-beta to reduce the molecular defect is being examined. LPS treatment of cultured cardiac myocytes induces expression of collagenase mRNA and this induction is abolished by TGF- beta.